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Joint Hospital Surgical Grand Round. Radiofrequency Ablation of Hepatic Tumor (Factors affect local recurrence rate) Dr K Y Yuen United Christian Hospital. Introduction. Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world
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Joint Hospital Surgical Grand Round Radiofrequency Ablation of Hepatic Tumor (Factors affect local recurrence rate) Dr K Y Yuen United Christian Hospital
Introduction • Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world • Global annual incidence is one million new patients • 70% in Asia and 12% in Africa
Introduction • Surgery is the only known curative option for either primary or secondary hepatic carcinoma • Resection or transplantation is the gold standard of treatment for liver tumor • Only 20% to 37% of patients is suitable for hepatectomy Fan et la, Annals of Surgery 1999
Introduction Factors limit the surgical intervention: • multiple / diffuse tumors • tumor in unresectable locations (proximity of the tumors to major vascular and biliary structures) • Poor co-morbidity • inadequate liver reserve • significant portal hypertension 5- year survival rate for resectable HCC or liver metastasis is only 20 - 40 % Loco-regional therapies have been developed for the treatment of unresectable liver tumor
Radio Frequency Ablation • First described by Rossi et al in 1993 • High-frequency (450- 500KHz) alternating RF current causes oscillatory movement of ions in tissue • The mechanism of tissue heating is frictional heat caused by the motion from the ionic current • Cause coagulation necrosis at temperature between 50-80oC
Radio Frequency Ablation Indications: • Alterative to surgery in poor liver function patient with primary or secondary liver tumor • Supplementary to surgery in bilobal tumors • Liver transplant candidates (bridge) Some transplant surgeons are using percutaneous or laparoscopic RFA to treat HCCs detected in patients with cirrhosis on the transplant waiting list in an attempt to attain local control of tumor and prevent progression Robert Goldstein, MD, personal communication, April 2000
Radio Frequency Ablation Contraindications: • Child’C cirrhosis (gross ascites) • Excessive tumor burden • Extrahepatic diseases • Active infection • Renal insufficiency • Coagulopathy • Near major ductal confluence
Radio Frequency Ablation • Complications (0-12%): • Abscess formation • Bleeding(delayed bleeding into the ablated area, subcutaneous/ subcapsular haematoma) • Needle tract seeding (up to 12.5%) • Bile leakage • Bile duct stricture • hydropneumothrorax • Liver failure • Grounding pad burn • Acute renal failure • Mortality: 0 -1%
Radio Frequency Ablation • RFA may be a superior option amount the locoreginal ablation therapy: Lower complication rate Less recurrence rate Shorter hospital stay R Poon et la, Annals of Surgery 1999
Radio Frequency Ablation Question to answer • What determine the efficacy of RFA in liver tumor patient ? • Local Recurrence is one of the important aspects Local recurrencewas defined as radiological (CT, MRI or contrast-enhanced ultrasound) and/or histological (tumor cells with intact mitochondrial enzyme staining) detection of residual or recurrent viable tumor at the site of the original tumor, during follow-up and after completion of all (one or more) sessions.
Pre OT Post OT 3 months Siperstein A et la, Annals of Surgical Oncology 2005 Post OT 1 week
Local Recurrence After Hepatic Radiofrequency CoagulationMultivariate Meta-Analysis and Review of Contributing Factors Stefaan Mulier, MD, Yicheng Ni, PhD, Jacques Jamart, MD,Theo Ruers, PhD, Guy Marchal, PhD, and Luc Michel, MD Annals of Surgery, August 2005
Local Recurrence • Local recurrence rate after RFA of liver tumors varies widely between 2% and 60% • A local recurrence seriously jeopardizes the chances of cure • Re-treatment is often impossible or has a high risk of failure • From Solbiati L et al 1999, only 55% recurrent tumors were re-treated and a complete coagulation was obtained in only cases 36%. • Reasons for not considering re-treatment: unfavorable geometry diffuse metastases
Local Recurrence Rate: Univariable Analysis of Contributing Factors • 9 factors: Diameter (size) Pathology Proximity of major vessel Location Approach(surgery Vs percutaneous) Intentional Margin Vascular occlusion Anaethesia Imaging Physician’s experience
Diameter (Size) • Current recommended tumor size <5cm • Nearly all authors agree tumor size determining local recurrence /efficacy • Goletti O et al, Montorsi M et al , Livraghi T et al, showed that complete tumor necrosis in 80% to 90% of HCCs smaller than 3 to 5 cm • Livraghi T et al, complete ablation rate for larger tumors is less favorable: a study of RFA for 126 HCCs 3.1 to 9.5 cm (mean 5.4 cm) reported a complete necrosis rate of 48% with the use of a clustered electrode.
Diameter (Size) Size of individual RFA is limited • Single coagulation cannot cover a large lesion i.e.< 100% necrosis – higher risk of local recurrence Adam R et la, Arch Surg 2002 • For large tumors, overlapping coagulations is necessary, however, technically difficulty –Ultrasonogram is difficult to visualize the tumor after 1st coagulation – hyperechoeic microbubble cloud R Poon et la, Annals of Surgery 2000
Diameter (Size) Large tumors have irregular borders and present satellite lesions Livraghi T et la, Radiology 2000 • If the coagulation is restricted to the main tumor without safety margin, spiky irregular extensions and satellites will be left untreated.
Effect of Tumor Size on Outcome of RF Ablation Livraghi T et al. Hepatocellular carcinoma: radio-frequency ablation of medium and large lesions. Radiology 2000; 214:761–768.
Diameter (Size) Conclusion • There is no consensus for the optimal size for RFA • Smaller tumor size ( < 3 cm diameter ), the better the outcome, the lesser the local recurrance rate • Due the advancing technology, future electrode may tackle with larger tumor
Approach • Surgical (open / laparoscopic) Vs Percutaneous • Absence of RCT • No consensus
Surgical (open / laparoscopic) Vs Percutaneous • From Steven A. Curley et la, complete ablations in the 65 HCCs treated during laparotomy or laparoscopy, however, 7.1% (6/84) incidence of incomplete RFA in the HCCs treated percutaneously. • From Rhim H et al, incomplete tumor destruction has been reported in up to 18% of liver cancers treated percutaneously with RFA
Surgical (open / laparoscopic) Vs Percutaneous • One disadvantage to RFA is the difficulty in determine accurately the exact area that has been coagulated • Intraoperative or laparoscopic ultrasonography provides better resolution of the tumor and RFA treatment compared with transabdominal ultrasonography for percutaneous treatment Steven A. Curley et la, Annals of Surgery 2000
Surgical (open / laparoscopic) Vs Percutaneous • Better tumor visualization compared with external ultrasound especially of tumors located in the superior right lobe of the liver • ~30% increase in tumor detection rate by intraoperative ultrasound during laparoscopy or laparotomy compared with preoperative imaging Siperstein T et la, Annals of Surgical Oncology 2002 • Accurate tumor staging K K-C Ng et la, Journal of Gastro-Hepatology 2003
Surgical (open / laparoscopic) Vs Percutaneous • Easy access to tumors located in the superior right lobe of the liver • Improved visibility will lead to a more correct insertion of the electrodes and an increased chance of complete covering of the tumor, including its irregular margins, satellites, and a 1-cm safety margin • Mobilization of the liver allows larger degree of freedom for inserting the electrodes under an optimal angle Rossi S et la, AJR AM J Roent-genol. 1996
Surgical (open / laparoscopic) Vs Percutaneous • Laparoscopic approach, pneumoperitoneum and the upward movement of the diaphragm, liver movement is minimal, facilitating precise electrode placement. Siperstein A et la, Surgical Endoscopy 2002 • Surgical route, allows multiple parallel reinsertions of the electrode when overlapping coagulations are necessary Rossi S et la, AJR AM J Roent-genol. 1996
Surgical (open / laparoscopic) Vs Percutaneous • Intraoperative RFA allows the use of Pringle maneuver to minimize the “heat sink” effect of the hepatic vessels Mulier S et la, Eur J Surgical Oncology 2003 • During laparoscopy, a 12-mm Hg pneumoperitoneum by itself causes a 40% decrease of portal vein flow Smith MK et la, Surgical Endoscopy 2004
A 5-cm hepatocellular carcinoma at the dome of the liver (A,arrow) treated by intraoperative radiofrequency ablation using a clustered probe (B). R Poon et la, Annals of Surgery 2002
Intraoperative ultrasound provides guidance to positioning of the probe (C, arrow shows the tip of the probe) in the tumor before starting radiofrequency ablation, but the exact margin of ablation is obscured by hyperechoic shadow resulting from thermal changes in the tissue after starting the ablation (D, arrows). R Poon et la, Annals of Surgery 2002
Surgical (open / laparoscopic) Vs Percutaneous • Intended safety margin of 1 cm, was used much less in the percutaneous approach than in the surgical approach • Subcapsular tumors are often undertreated by a percutaneous approach because of fear of burning adjacent organs, diaphragm, or the abdominal wall R Poon et la, Annals of Surgery 2002
Surgical (open / laparoscopic) Vs Percutaneous tumor 10 mm Intentional Margin According to Approach Ablation zone
Surgical (open / laparoscopic) Vs Percutaneous Conclusion • Laparoscopic or open approach is recommended in patients with a high risk of bleeding from severe coagulopathy, large HCCs (5 cm), superficial nodulesadjacent to other visceral organs at risk of thermal injury, or deeply located lesions not accessible to percutaneous puncture R Poon et la, Annals of Surgery 2002
Surgical (open / laparoscopic) Vs Percutaneous • The percutaneous route remains valuable for certain indications: For patients that are too fragile to undergo laparoscopy or laparotomy. Tumors that are invisible on ultrasound imaging can be treated by a CT- or MRI-guided percutaneous procedure. May be performed as a day procedure
Percuteneous (%) Laparoscopy/ Laparotomy (%) <3 cm 16.0 3.6 3-5 cm 25.9 21.7 >5 cm 60.0 50.0 Local Recurrence Rate According to Size and Approach Surgical (open / laparoscopic) Vs Percutaneous
Conclusion • Surgery remain the gold standard of treating liver tumor • RFA is superior option in treating unresectable primary and secondary • Surgical approach have less local recurrance rate and better outcome when compared with percutaneous route • Small size tumor have better outcome, however, advance technology may overcome this problem in future
RFA Vs Cryoablation • Local recurrence rate: • 2.2% Vs 13.6% • Treatment mortality: • 0% Vs 2% • Complication rate: • 3.3% Vs 40% Pearson AS et al. Am. J. Surg. 1999
RFA Vs Microwave Coagulation Therapy • Complete ablation: • 91% Vs 85% • Local recurrence • 4%Vs 17% Lencioni et al. Radiology 1999
RFA Vs PEI • Complete necrosis : • RFA Vs PEI – 90% Vs 80% • Treatment section: • Mean 1.2 Vs 4.8 sessions • Complication rate: • 12% Vs 0% Livraghi T et al. Radiology 1999
RFA Vs TACE • Complete control of tumor growth: • 50% Vs 30% • Mortality: • 0% Vs 4% Livraghi et al. Radiology 2002
RFA Vs Resection • Recurrence • 53% Vs 30% • Resection recurrence – distant recurrence • RFA recurrence – local recurrence Montorsi M et la, The Society for Surgery of the Alimentary Tract 2005 • Resection is more effective, in terms of overall and disease-free survival, in Child’s A patient with a singletumour >3cm Vivarelli M et la, Annals of Surgery 2004
RFA – Bridge therapy • Retrospective study • 14 cirrhotic patients with small HCC ( 3.5cm) • RFA prior to transplanatation • Median follow-up: 16 months • Histology : • complete necrosis: 71% • incomplete necrosis: 29% • tumour satellites < 1cm from main tumour: 57% • No complication/ death/ recurrence